Using the hydrolysis of anhydrides to control gel properties and homogeneity in pH-triggered gelation

The pH of an aqueous solution of a low molecular weight gelator can be adjusted through the hydrolysis of a number of anhydrides to the corresponding acids. The rate of hydrolysis and hence of pH change can be used to control the rate of gel formation. This rate does not affect the primary assembly of the low molecular weight gelator, but does affect the mechanical properties of the resulting gels, as well as the homogeneity and reproducibility of the gels. The mechanical properties are compared by both rheology and dynamic nanoindentation

Controlling the assembly and properties of low-molecular-weight hydrogelators

Low-molecular-weight gels are formed by the self-assembly of small molecules into fibrous networks that can immobilize a significant amount of solvent. Here, we focus on our work with a specific class of gelator, the functionalized dipeptide. We discuss the current state of the art in the area, focusing on how these materials can be controlled. We also highlight interesting and unusual observations and unanswered questions in the field

Relating the chemical reactivity of supramolecular hydrogelators and the physical properties of their gels

This thesis reports a number of studies that examines low molecular weight hydrogelators forming through in situ chemical reactions and gel the water in which this reaction occurs. This in situ gelation process has allowed a number of chemical and physical reactions and assembly processes to be investigated. Pathway complexity, an exciting concept within chemical systems has been explored with a multi-reactive hydrazone based gelation system that allows different gels to be formed from a single starting point through navigation of the systems’ energy landscape. This work inspired the development of a large family of imine based gelators that would undergo an effectively irreversible tautomerisation. This allowed exploration and characterisation of the systems’ ability to self-sort and co-assemble, at both the molecular and macroscopic level. One particular imine inspired gelator featured a much slower in situ reaction. This allowed characterisation of its reaction kinetics and demonstrated its autocatalytic behaviour. This thesis highlights the link between the chemical reactions that form the individual gelator molecules and the supramolecular assembly process. By using one to control the other, an in-depth understanding of the presented systems has been developed, allowing for the accurate targeting of desired physical properties

Photoresponsive gelators

Low molecular weight gels can be responsive to a range of external stimuli. The use of light as an external stimulus to modify gels is of particular interest for a number of reasons. Light is a non-invasive trigger. For example, using light it is possible to spatially target a specific area of the gel leading to patterned gel surfaces. Here, we review the different approaches that have been used to form low molecular weight gels that respond to ligh

Novel Oligomeric Biodegradable Crosslinkers For Hybrid Biomaterial Fabrication For Regenerative Purposes

INTRODUCTION Increasing age of population is a great success of numerous breakthroughs in life science and improved health care. For a child born in 2015, for example, an average global life expectancy of meanwhile 71.4 years is assumed which increased by around 8% in the last decade [1]. In accordance with enhanced life expectancy, however, age-related health problems continuously rise. In this regard, the gap between patients awaiting transplantation and appropriate donors consequently will get larger in the future [2]. To this end, there is a need for new strategies in regenerative medicine [3]. Biomaterial matrices were developed to foster tissue regeneration by mimicking the key characteristics of the extracellular matrix (ECM) [4]. Modern biomaterial research focuses on 3D scaffolds, which can be adequately adapted toward specific requirements of the target tissue [5]. In this regard, flexible material platforms are wanted, whose properties can be adjusted over a wide range and independently of each other [6]. In this context, the macromer-based material concept is promising due to the high flexibility of macromers in chemical design and processability [7]. Macromers are reactive oligo- or polymeric molecules which act as monomers and can therefore be polymerized/cross-linked into a polymeric network [8]. The key principle of this approach is the synthesis of chemically well-defined structures which allows for a more precise control over the resulting properties of the cross-linked polymeric network when compared to conventional polymers. For example, macromer chemistry can be adjusted in terms of chemical macromer composition, valence, content of cross-linkable functionalities and molecular weight. The versatility of macromer-derived materials greatly increases when different macromer types are combined which potentially enables precise material tunability on multiple levels. The design flexibility of macromer-based networks motivated the investigation of two different macromer-based material concepts with regard to macromer processability and material adjustability. The following objectives were proposed: 1) To synthesize two sets of biodegradable, multi-valent macromers by using free-radical polymerization and ring-opening polymerization combined with established activation strategies. The synthesis setups will be tuned toward high macromer yields which will be required for processing into biomaterials with relevant sizes. 2) To physico-chemically characterize oligomeric macromers with regard to chemical composition, molecular weight and reactivity in order to yield well-defined macromer structures. NMR spectroscopy, gel permeation chromatography (GPC) and wet chemistry will be applied. 3) To characterize macromer processability into covalently cross-linked hybrid matrices. This work will focus on a soft macromer-cross-linked gelatin-derived hydrogel system for versatile biomedical applications as well as a rigid macromer/sol-gel glass hybrid material for hard tissue regeneration. Sets of different formulations will be investigated in order to characterize the range of macromer processability and to establish structure-property relationships. 4) To investigate strategies for the adjustment of material porosity. Besides the adaption via cross-linking density, porogen-leaching and 3D-printing approaches will be followed in order to introduce macroporosity and to enable a decoupling of porosity and chemical (nano)structure of the cross-linked network. 5) To determine key material properties relevant for regenerative applications, including mechanical properties by compression tests and oscillation rheology, in vitro matrix degradability, as well as material cytocompatibility in indirect and direct contact experiments. 6) To identify strategies for covalent functionalization of the hybrid materials. Post-fabrication functionalization via specifically introduced chemical functionalities is favored as it enables effective material decoration (almost) independent of the physico-chemical matrix properties. SUMMARY OF DISSERTATION The first material concept was based on anhydride-containing macromers which can be processed into hydrogel matrices by covalent cross-linking of amine-bearing macromolecules, such as gelatin [9–11]. The innovative aspect of this work was to decouple material functionalization from the physico-chemical properties of the cross-linked hydrogel network. To this end, a second chemical functionality was introduced which remained reactive in the hydrogel state and was therefore available for covalent post-fabrication functionalization strategies. Specifically, dual-functional macromers were synthesized by free-radical polymerization of maleic anhydride (MA) with diacetone acrylamide (DAAm) and pentaerythritol diacrylate monostearate (PEDAS) to yield oligo(PEDAS-co-DAAm-co-MA) (oPDMA) [12]. Amphiphilic oligomers (molecular weight (Mn) < 7.5 kDa) with anhydride contents of 7-20% were obtained. Fractions of chemically intact anhydrides of around 70% enables effective cross-linking with low molecular-weight gelatinous peptides (Collagel® type B, 11 kDa). Rigid two-component hydrogels (elastic modulus (E) = 4-13 kPa) with adjustable composition and physicochemical properties were formed. Reactivity of the incorporated methyl ketone functionality toward hydrazides and hydrazines was shown on the macromer level and in the cross-linked hydrogel by different strategies. Firstly, pre-fabricated hydrogels were successfully reinforced by secondary cross-linking with adipic acid dihydrazide (ADH). Secondly, pH-dependent immobilization of 2,4-dinitrophenylhydrazine (DNPH) to acid-soluble macromer derivatives as well as cross-linked oPDMA/COL matrices was demonstrated. Thirdly, reversible immobilization of a fluorescent hydrazide (AFH) was shown which was controlled by hydrogel ketone content, hydrazide ligand concentration and medium pH. This triple-tunability of hydrazide immobilization holds promise for adjustable and cost-effective hydrogel modification. Lastly, proof-of-concept experiments with hydrazido-functionalized hyaluronan (ATTO-hyHA) demonstrated the potential for covalent post-fabrication hydrogel decoration with ECM components. Hydrogel cytocompatibility was demonstrated and the introduction of DAAm into the hydrogel system resulted in superior cell material interactions when compared with previously established analogous ketone-free gels [13]. Limited ability of cells to migrate into deeper regions of these macromer-cross-linked gelatin-based gels further motivated the investigation of two different strategies to enhance hydrogel porosity [10,14]. On the one hand, the introduction of macropores was attempted by hydrogel fabrication in presence of poly(ethylene glycol) (Mn = 8000 Da, P8k). This polymer acted as porogen by phase separation during hydrogel formation. It was found that P8k was effectively extracted from the cross-linked matrix, while physico-chemical hydrogel properties remained unchanged. The second approach aimed at increasing mesh size of the cross-linked network by using hydrogel building blocks with increased molecular weights. In particular, high molecular-weight gelatin (160 Bloom, G160) was cross-linked by macromers with low MA content. Homogeneous and mechanically stable hydrogels were obtained and physico-chemical properties were determined. Successful optimization of hydrogel porosity was functionally shown by enhanced cell migration and improved release profile of incorporated nanoparticles [15]. In the second macromer-based material, hydrolytically degradable multi-armed macromers were covalently introduced into a tetraethoxysilane(TEOS)-derived silica sol in order to address the insufficient degradability of glass-based materials [16]. In detail, oligo(D,L-lactide) units were introduced into three- (TMPEO, Tx) and four-armed (PETEO, Px) ethoxylated alcohols by ring-opening polymerization, followed by activation with 3-isocyanatopropyltriethoxysilane (ICPTES) to yield TxLAy-Si and PxLAy-Si macromers [17,18]. A series of 18 oligomers (Mn: 1100-3200 Da) with different degrees of ethoxylation and varying length of oligoester units was synthesized. Applicability of a previously established indirect rapid prototyping method enabled fabrication of macromer/sol-gel-glass-derived class II hybrid scaffolds with controlled porosity [19]. Successful processability of a total of 85 different hybrid scaffold formulations allowed for identification of relevant structure-property relationships. In vitro degradation was analyzed over 12 months and a continuous linear weight loss (0.2-0.5 wt%/d) was detected which was controlled by oligo(lactide) content and matrix hydrophilicity. Compressive strength (2-30 MPa) and compressive modulus (44-716 MPa) were determined and total content, oligo(ethylene oxide) content, oligo(lactide) content and molecular weight of the oligomeric cross-linkers as well as material porosity were identified as the main factors determining hybrid mechanics by multiple linear regression. Cell migration into the entire scaffold pore network was indicated in cell culture experiments with human adipose tissue-derived stem cells (hASC) and continuous proliferation over 14 days was found. Overall, two macromer-based material platforms were established in which material versatility was realized by three main principles: I) synthesis of macromers with different chemical composition, II) combination of macromers with a second oligomeric building block, and III) flexible processability of these dual-component hybrid formulations into porous scaffold materials. Precise adjustability of material properties as demonstrated in both concepts offers potential for application of these hybrid materials for a wide range of regenerative purposes. REFERENCES (1) World Health Statistics of the WHO. http://www.who.int/gho/publications/world_health_statistics/en/ 2017. (2) OPTN/UNOS Public Comment. https://optn.transplant.hrsa.gov/ 2017. (3) Puppi, D.; Chiellini, F.; Piras, a. M. M.; Chiellini, E. Prog. Polym. Sci. 2010, 35 (4), 403–440. (4) Patterson, J.; Martino, M. M.; Hubbell, J. A. Mater. Today 2010, 13 (1–2), 14–22. (5) Picke, A.-K.; Salbach-Hirsch, J.; Hintze, V.; Rother, S.; Rauner, M.; Kascholke, C.; Möller, S.; Bernhardt, R.; Rammelt, S.; Pisabarro, M. T.; Ruiz-Gómez, G.; Schnabelrauch, M.; Schulz-Siegmund, M.; Hacker, M. C.; Scharnweber, D.; Hofbauer, C.; Hofbauer, L. C. Biomaterials 2016, 96, 11–23. (6) Loth, R.; Loth, T.; Schwabe, K.; Bernhardt, R.; Schulz-Siegmund, M.; Hacker, M. C. Acta Biomater. 2015, 26, 82–96. (7) DeForest, C. A.; Anseth, K. S. Nat. Chem. 2011, 3 (12), 925–931. (8) Nic, M.; Jirát, J.; Košata, B.; Jenkins, A.; McNaught, A.; Wilkinson, A. IUPAC, Research Triangle Park, NC 2014. (9) Loth, T.; Hennig, R.; Kascholke, C.; Hötzel, R.; Hacker, M. C. React. Funct. Polym. 2013, 73 (11), 1480–1492. (10) Loth, T.; Hötzel, R.; Kascholke, C.; Anderegg, U.; Schulz-Siegmund, M.; Hacker, M. C. Biomacromolecules 2014, 15 (6), 2104–2118. (11) Kohn, C.; Klemens, J. M.; Kascholke, C.; Murthy, N. S.; Kohn, J.; Brandenburger, M.; Hacker, M. C. Biomater. Sci. 2016, 4, 1605–1621. (12) Kascholke, C.; Loth, T.; Kohn-Polster, C.; Möller, S.; Bellstedt, P.; Schulz-Siegmund, M.; Schnabelrauch, M.; Hacker, M. C. Biomacromolecules 2017, 18 (3), 683–694. (13) Sülflow, K.; Schneider, M.; Loth, T.; Kascholke, C.; Schulz-Siegmund, M.; Hacker, M. C.; Simon, J.-C.; Savkovic, V. J. Biomed. Mater. Res. A 2016, 104 (12), 3115–3126. (14) Loth, T. Diss. Univ. Leipzig, Fak. für Biowissenschaften, Pharm. und Psychol. 2016. (15) Schwabe, K.; Ewe, A.; Kohn, C.; Loth, T.; Aigner, A.; Hacker, M. C.; Schulz-Siegmund, M. Int. J. Pharm. 2017, 526 (1–2), 178–187. (16) Rahaman, M. N.; Day, D. E.; Sonny Bal, B.; Fu, Q.; Jung, S. B.; Bonewald, L. F.; Tomsia, A. P. Acta Biomater. 2011, 7 (6), 2355–2373. (17) Schulze, P.; Flath, T.; Dörfler, H.-M.; Schulz-Siegmund, M.; Hacker, M.; Hendrikx, S.; Kascholke, C.; Gressenbuch, M.; Schumann, D. Ger. Pat. No. DE102014224654A1 2016. (18) Kascholke, C.; Hendrikx, S.; Flath, T.; Kuzmenka, D.; Dörfler, H.-M.; Schumann, D.; Gressenbuch, M.; Schulze, F. P.; Schulz-Siegmund, M.; Hacker, M. C. Acta Biomater. 2017, 63, 336–349. (19) Hendrikx, S.; Kascholke, C.; Flath, T.; Schumann, D.; Gressenbuch, M.; Schulze, P.; Hacker, M. C.; Schulz-Siegmund, M. Acta Biomater. 2016, 35, 318–329

Controlling Visible Light-Driven Photoconductivity in Self-Assembled Perylene Bisimide Structures

Alanine-functionalized perylene bisimides (PBI-A) are promising photoconductive materials. PBI-A self-assembles at high concentrations (mM) into highly ordered wormlike structures that are suitable for charge transport. However, we previously reported that the photoconductive properties of dried films of PBI-A did not correlate with the electronic absorption spectra as activity was only observed under UV light. Using transient absorption spectroscopy, we now demonstrate that charge separation can occur within these PBI-A structures in water under visible light. The lack of charge separation in the films is shown by DFT calculations to be due to a large ion-pair energy in the dried samples which is due to both the low dielectric environment and the change in the site of hole-localization upon drying. However, visible light photoconductivity can be induced in dried PBI-A films through the addition of methanol vapor, a suitable electron donor. The extension of PBI-A film activity into the visible region demonstrates that this class of self-assembled PBI-A structures may be of use in a heterojunction system when coupled to a suitable electron donor

Investigating the self-assembly process in supramolecular hydrogels

Supramolecular hydrogel materials, which form via the assembly of low molecular weight gelators, have represented a developing field of research that is showing signs of maturing into an impactful research subject. However, a thorough understanding of the assembly process is crucial for a more wide-spread use. Within this work, control over the assembly mechanism in multicomponent gels and the exploration of the thermodynamics surrounding the assembly of a light-triggered hydrogel are explored. The assembly mechanisms operating in four multicomponent triformylphloroglucinol based hydrogels was confirmed primarily by using small-angle neutron scattering but with support from rheological experiments, wide angle x-ray diffraction and molecular dynamics simulations. The effect of using different aromatic substituents was investigated and their electronic nature was found to greatly influence the assembly. Furthermore, two distinct gelation routes were probed which allowed the synthesis of two different gels from the same initial components by controlling the assembly mechanism with dynamic covalent chemistry. Distinguishing the underlying causes for changes in the mechanisms allows for the elucidation of design principles which can, in future, be applied to similar systems. Control over the assembly mechanism allows for the tailoring of the gels for specific applications with photooxidation being explored within this work. Seven visible-light harvesting gelators were synthesised by attachment of different organic photosensitisers and their efficiency in the production of singlet oxygen was probed using the oxidation of methionine as a test reaction. Taking cues from Nature, synthetic systems which operate out-of-equilibrium have become an active area of research. This work aims to further advance this field with the incorporation of photochemistry, employing singlet oxygen mediated reactions as a trigger for assembly. Such reactions require only oxygen from air, light of the appropriate wavelength and a photosensitiser, which in great part circumvents the need for toxic reagents whilst also avoiding the build-up of waste. A meta-stable gel was formed by designing a gelator with a singlet oxygen sensitive moiety which can be used to trigger gelation. The equilibrium between the gel and solution state was subsequently controlled by altering the pH and salt concentration of the system

Exploring mucoadhesive and toxicological characteristics of novel water-soluble polymers synthesised by modifying linear polyethyleneimine with various anhydrides

Linear polyethyleneimine (L-PEI) has been extensively used in various fields, such as pharmaceutical formulations, gene delivery, and water treatment. Though L-PEI is considered as a potential gene delivery vector or as a pharmaceutical excipient, the applications of L-PEI are limited as L-PEI displays relatively high toxicity and low biocompatibility. The secondary amine groups within L-PEI can interact with cell membranes and the extracellular matrix, and these interactions are predominantly electrostatically driven. Herein, we selected succinic anhydride, phthalic anhydride, methacrylic anhydride, crotonic anhydride and maleic anhydride to modify L-PEI to improve functionality and lower its toxicity. Firstly, L-PEI was prepared by fully hydrolyzing commercially available poly(2-ethyl-2-oxazoline) (PEOZ, 50 kDa) and then reacted with different anhydrides. The obtained succinylated L-PEI, phthaylated L-PEI, methacrylated L-PEI, crotonylated L-PEI and maleylated L-PEI were fully characterized using 1 H-NMR and FTIR spectroscopies, turbidity-pH measurements and electrophoretic mobility. The resultant polymers (succinylated L-PEI, phthaylated L-PEI and maleylated L-PEI) were the polyampholytes which each have an isoelectric point (pHIEP), and two cationic polyelectrolytes methacrylated L-PEI, crotonylated L-PEI according to their structures. Water-soluble polymers generally exhibit mucoadhesive activity, interacting with mucin via electrostatic effects or hydrogen bonding or/and formation of interpenetrating layer between polymers and mucus gel. Mucoadhesion of polymers can provide significant opportunities when designing pharmaceutical formulations, such as tablets, films, patches and gels. However, the mucoadhesive properties of polyampholytes are rarely reported in the literature. This work thus explored the factors affecting the mucoadhesive properties of both synthetic and natural polyampholytes. Turbidimetric titrations and isothermal titration calorimetry (ITC) were conducted to investigate the interactions between polyampholytes and porcine gastric mucin in solutions. Both synthetic and natural polyampholyte demonstrated more pronounced interactions with mucin at pH<pHIEP than at pH≥pHIEP, where the polyampholytes are positively charged and mucin remains negatively charged. Electrostatic effects are predominantly responsible for their mucoadhesion whilst hydrogen bonding and hydrophobic effects have synergistic effects. A system of polyampholyte and fluorescein isothiocyanate (FITC) coated tablets were used to assess adhesion to porcine gastric mucosa at different pHs in essentially “static” systems. In addition, to reflecting fluid dynamics encountered on clinical application, the polyampholytes were labelled fluorescently and prepared in solutions to determine their retention using a fluorescence microscopy-based flow-through assay. These ex vivo assays confirmed that the polyampholytes exhibited superior mucoadhesive properties at pH<pHIEP. All these studies demonstrated solution pH and pHIEP of polyampholytes are primary factors affect mucoadhesive properties of polyampholytes, and hydrogen bonding, hydrophobic effects, water transport, capillary forces, penetration also contribute to mucoadhesion. To test the generalisability of these findings, the retention of methacrylated L-PEI, crotonylated L-PEI, maleylated L-PEI and succinylated L-PEI on bovine palpebral conjunctiva at physiological pH (pH=7.4) was assessed using a fluorescence microscopy-based flow-through assay. Methacrylated-L-PEI and crotonylated L-PEI exhibited strong mucoadhesive properties at pH 7.4, due to the formation of covalent bonding between unsaturated C=C moieties within these synthetic cationic polyelectrolytes and mucin thiol groups. Conversely, maleylated L-PEI and succinylated L-PEI were poorly-mucoadhesive since physiological pH was above their isoelectric point, leading to electrostatic repulsion between the polyampholytes and mucin. In addition, the contribution of amine groups within these polyelectrolytes to adhesion are minimal at pH=7.4, where these polyelectrolytes are either non-charged or negatively charged. Toxicological evaluation and irritation studies of the modified L-PEI derivatives were undertaken. In vivo assays with planaria and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay, and slug mucosa irritation assay suggested anhydride modified L-PEIs alleviated the adverse toxicity effects seen for the parent L-PEI. In summary, modification of L-PEI with organic anhydrides enhanced mucoadhesive properties and biocompatibility of L-PEI, and reduced its toxicity, displaying great potential of modified L-PEI derivates as novel water-soluble functional excipients for mucoadhesive delivery systems

Chemically Cross-Linked Polysaccharide-Based Hydrogels via Thiol-Norbornene Reaction as Sustainable Biomaterials

Hydrogels are 3D polymeric networks with high water content and are widely being investigated for biomedical applications such as tissue engineering. Polysaccharides have been used to fabricate hydrogels due to their natural abundance, biocompatibility, and immunogeniety. Additionally, polysaccharide-based hydrogels can provide mechanical and biological cues similar to those of the natural environments. In this work, thiol-norbornene chemistry was used to fabricate polysaccharide-based hydrogels including hyaluronic acid (HA), carboxymethyl cellulose (CMC), and cellulose nanofibrils (CNFs). Hydrogels with tunable physical and mechanical properties were achieved. The properties of these hydrogels were spatiotemporally modified by photopatterning. Also, high stem cell viability was achieved when cells were encapsulated in these hydrogels

Development of Biocomposites Based on Cellulosic Reinforcements

Les renforts cellulosiques sont une ressource renouvelable, biodégradable et biocompatible et leur faible densité ainsi que leur abondance élevée ont favorisé leur insertion dans les matrices polymères. Cependant, ces charges hydrophiles sont généralement incompatibles avec les matrices thermoplastiques communes non polaires telles que le polypropylène (PP) ou le polylactide (PLA). Le but de cette thèse est de développer des biocomposites possédant des propriétés mécaniques améliorées, à base de renforts cellulosiques. Dans la première phase de cette étude, les propriétés rhéologiques, mécaniques et morphologiques des composites polypropylène/fibres de lin ont été étudiées. Les polypropylènes greffés anhydride maléique (PPMA) ou acide acrylique (PPAA) ont été utilisés comme compatibilisants. Il a été montré que le malaxage à l’état fondu de ces composites entraîne une diminution de la longueur moyenne des fibres d'environ 70%. Par ailleurs, nous avons observé que l’ajout de compatibilisants, améliore l'interaction fibre/polymère et conduit à une plastification de la matrice. L'équilibre entre ces effets concurrents détermine le comportement rhéologique du composite. Le PPMA et le PPAA se sont avérés efficaces, mais leur efficacité dépend de leur indice de fluidité à chaud (MFI) et de leur teneur en groupements greffés. Les tests en traction ont montré que le module d’Young du composite contenant 30% en poids de fibres de lin est amélioré de 200% et que sa résistance à la rupture augmente de 60%, par rapport au PP. Le PPMA, ayant la teneur la plus élevée en groupements anhydrides maléiques, s'est avéré le plus efficace pour améliorer la compatibilité interfaciale entre la matrice PP et les fibres de lin, toutefois l'effet plastifiant de cet agent de couplage est significatif. Dans la seconde partie de ce travail, les propriétés rhéologiques, mécaniques, morphologiques et thermiques des composites PP/nanocristaux de cellulose (CNC), préparés par malaxage à l'état fondu ont été étudiées. Le PPMA a été utilisé comme compatibilisant pour ce système. Les influences de deux températures d’élaboration et de deux PPs de poids moléculaires différents ont été étudiées. Il a été montré qu’en présence de CNC la dégradation du PP à une température d’élaboration élevée avait un effet significatif sur le comportement rhéologique de ces systèmes. Lors des tests en traction, le module d’Young des composites contenant 2% en poids de CNC est amélioré d'environ 30% et leur résistance à la rupture est augmentée jusqu’à 16%, par rapport aux matrices seules. En revanche, la contrainte à la rupture des composites diminue de 17% à 75% par rapport à la matrice, en fonction des conditions d’élaboration et du poids moléculaire du PP. Dans le cas du PP de faible poids moléculaire, les composites élaborés à une température plus élevée ont montré de meilleures propriétés mécaniques. D'autre part, les meilleures propriétés mécaniques sont obtenues pour les composites à base de PP possédant un poids moléculaire élevé, élaborés à une faible température. L’extrusion bi-vis des composites à base de PP de faible poids moléculaire s’est avérée plus efficace que l'utilisation d'un mélangeur interne, pour l’élaboration de ces composites. Le module d’Young des composites PP/CNC peut être décrit par le modèle proposé par Nielsen, basé sur l'équation d’Halpin-Tsai. Enfin, il a été observé que les composites PP/CNC présentent une bonne ductilité, avec une augmentation de la contrainte à la rupture, par rapport au PP, comprise entre 43% et 73% PP, alors que les composites PP/fibres de lin sont fragiles, avec une contrainte à la rupture inférieure de 0,06 à celle de la matrice. Dans la dernière partie de cette thèse, l'état de dispersion des CNC et CNC modifiés (mCNC) a été étudié dans du diméthyl sulfoxyde (DMSO). Les mCNC ont été modifiés par greffage d'un chlorure d'acide organique à la surface des nanoparticules. L'efficacité de cette modification de surface est confirmée par spectroscopie de photoélectrons aux rayons X (XPS). A température ambiante, les propriétés rhéologiques des suspensions de CNC restent quasiment inchangées au cours du temps, alors qu’à une température de 70°C un gel se forme après un jour, même à une très faible concentration de CNC (1% en poids). Pour les suspensions contenant 3% en poids de CNC, la viscosité complexe mesurée à 70°C augmente de près de 4 décades après une journée. Pour les mCNCs dans du DMSO, un gel faible est formé à partir du premier jour et la température n'a pas affecté la gélification et l’évolution de la viscosité complexe est faible, après un jour. Les propriétés rhéologiques des gels de mCNC à 70°C sont largement plus faibles que celles des gels de CNC. Enfin, l'ajout de 10% en poids de polylactide (PLA) au milieu ne prévient pas la formation de gels pour les suspensions CNC. De plus, la viscosité et le module de stockage réduits des suspensions de CNC et de mCNC dans un milieu PLA/DMSO sont considérablement inférieurs à ceux des échantillons sans PLA. Ce résultat a été attribué aux mauvaises interactions entre les nanoparticules et les chaînes de PLA et à la diminution du mouvement brownien des nanoparticules, due à l'augmentation de la viscosité du milieu de la suspension. Au meilleur de nos connaissances, c'est la première fois que la gélification des suspensions de CNC et de mCNC, avec une très faible teneur en solvant polaire non aqueux et non-toxique comme le DMSO, a été étudiée. ---------- Interesting properties of cellulosic reinforcements such as their low density, renewability, biodegradability, absence of health hazard and high abundance have favored their use in polymer composites. The key issue for polymer composites based on cellulosic reinforcements is the incompatibility between these hydrophilic fillers and non-polar common matrices such as polypropylene (PP) or polylactide (PLA). The main objective of this dissertation is to develop polymer biocomposites with enhanced mechanical properties based on cellulosic reinforcements. In the first phase the rheological, mechanical and morphological properties of flax fiber polypropylene composites were investigated. PP grafted maleic anhydride (PPMA) and PP grafted acrylic acid (PPAA) were utilized as compatibilizers. Compounding resulted in a decrease of the mean fiber length by about 70%. It has been observed that both compatibilizers, besides enhancing fiber/polymer interaction, can lead to plasticization and the balance between these competing effects determined the overall rheological behavior of the composite. PPMA and PPAA were effective compatibilizers for PP/flax fiber composites, but their efficiency depended on their melt flow index (MFI) and grafted group content. The tensile modulus of the composite containing 30 wt% flax fibers was improved by 200% and the tensile strength improved by 60% in comparison with the neat PP. The PPMA with the highest content of MA was found to be the most efficient in improving the interface between the PP matrix and the flax fibers, however the plasticizing effect of this coupling agent was significant. In the second phase the rheological, mechanical, morphological and thermal properties of PP/cellulose nanocrystal (CNC) composites prepared in the molten state were investigated. PPMA was used as a compatibilizer for this system. The effect of two different processing temperatures with two different molecular weight PPs has been investigated. Degradation of the PP in the presence of CNCs at high processing temperature was shown to have a significant effect on the rheological behavior. The tensile modulus of composites containing 2 wt% CNCs was improved by about 30% and the tensile strength was increased up to 16%, in comparison with the neat matrices. The tensile strain at break of the composites decreased by 17% up to 75% with respect to the matrix, depending on the processing conditions and PP grade. For low molecular weight PP the composites processed at higher temperature showed better mechanical properties. On the other hand, better mechanical properties were obtained for the high molecular weight PP-based composites processed at lower processing temperature. Preparing the low molecular weight PP composites via twin-screw extrusion was shown to be more efficient than using an internal batch mixer. The tensile modulus of the PP/CNC composites could be fairly well described by a model proposed by Nielsen based on the Halpin-Tsai equation. Finally, it was observed that the PP/CNC composites exhibited a good ductility, with their strain at break varying between 43 and 73% of the PP value in comparison to the PP/ flax composites, which were brittle and their strain at break was less than 0.06 of that of the matrix. In the last phase, the potential use of dimethyl sulfoxide (DMSO) as a dispersing medium for CNCs and modified CNCs (mCNC) was investigated. Cellulose nanocrystals have been modified via grafting an organic acid chloride on the surface of the nanoparticles. The efficiency of surface modification has been confirmed by X-ray photoelectron spectroscopy (XPS). The rheological properties of CNC suspensions did not change significantly with time at room temperature, but the CNC suspensions at 70 °C underwent gel formation, even at a very low concentration (1 wt%) after one day. For suspensions containing 3 wt% CNCs, the complex viscosity at 70 °C increased by almost 4 decades after one day. For the mCNCs in DMSO a weak gel was formed from the first day and temperature did not affect the gelation and changes in the complex viscosity after one day were marginal. The rheological properties of the mCNC gels at 70 °C were found to be much lower than those of the CNC gels. Finally, the effect of adding 10 wt% of polylactide (PLA) to the solvent on the rheological properties of CNC and mCNC suspensions was investigated. PLA did not prevent gel formation for the CNC suspensions. However, the reduced viscosity and storage modulus of the CNC and mCNC suspensions in PLA/ DMSO were considerably lower than those of samples without PLA. This has been attributed to poor interactions between the nanoparticles and the PLA chains and the decreased influence of the Brownian motion due the increased viscosity of the suspending medium. To the best of our knowledge this is the first time that the gelation of CNC and mCNC suspensions at very low content in a polar non-aqueous, safe solvent like DMSO has been investigated